Are you currently (or have you been) in a Clinical Trial?

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  • irishlove
    irishlove Posts: 800

    "The Dr. Using AI To Find Hidden Cures" by Ryan D'Agostino

    I found a lengthy but fascinating story in my Apple feed today regarding Castleman's Disease and Dr. David Fajgenbaum. Dr. David was working towards becoming an oncologist when he became ill with Castlemans. He developed non-profit programs thru U of Penn to match already existing drugs to diseases. It was fascinating and then when I got to a certain paragraph, well I made my husband come listen. Dr. David mentioned one of the drugs matched to improved outcomes for breast cancer and mets was, lidocaine. I had never heard of this before, but it's been approved and is in use. Please if you have chance read this story. Of note it mentioned TNBC improvements when lidocaine was combined with chemo drugs.

    Irishlove

  • cure-ious
    cure-ious Posts: 3,194
    edited April 10

    For those interested, the abstracts for the AACR 2026 meeting, starting next week, are online and search-able, here is one describing combination of KAT6 and PIK3CA inhibitors:

    https://aacrjournals.org/cancerres/article/86/7_Supplement/4499/777433/Abstract-4499-KAT6i-prifetrastat-combines-with?searchresult=1

  • eleanora
    eleanora Posts: 614

    Thanks cure-ious. I appreciate all of the sources you share. I currently have no actionable mutations, but will file this away for the future. My CEA has been rising slowly for the past three months (now at 48), so I will be ending my 4 year run on Kisqali. Have not met with MO yet, but she previously advised that my options were Verzenio or Affinitor with Xeloda after that. Trying to do my research before next Friday's appointment.

  • cure-ious
    cure-ious Posts: 3,194
    edited July 9

    Here's an interesting trial, trying to collect some hard numbers on the outcomes for those with Her2-positive cancers who take a drug holiday of at least 3 months (median was 14 months), often because of toxicity but also patients choice.

    Not surprisingly, there was a benefit for those who had gotten a complete response (all tumors shrunk) or partial response (at least 30% shrinking on average of tumors) from their therapy, but the significance was encouraging and gives some guidance for those considering it

    https://www.cancernetwork.com/view/84-exceptional-responders-in-de-novo-metastatic-breast-cancer-dnmbc-drug-cessation-in-patients-with-her2-positive-metastatic-breast-cancer-multicenter-retrospective-study

  • bsandra
    bsandra Posts: 1,106

    Dear @cure-ious , what an interesting article (sorry, have been on a holiday, so writing only now)! It is still very sad that even ExR died:/ It would be important to see the timelines, i.e. when people have gotten their best responses confirmed, then when they went off the therapy, and then when relapses happened and/or who marches on… Saulius

  • cure-ious
    cure-ious Posts: 3,194
    edited October 24

    At ESMO 2026 today, Hope Rugo presented the results of the phase III Keynote-B49 trial, which tested the effects of adding Keytruda to physicians-choice chemo (Xeloda, Enhertu, etc) for those with ER-positive cancer that has some detectable expression of the PDL-1 antigen. The other requirement was that this would be the first chemo the patient had following endocrine therapy, because strongly estrogen-dependent cancers have immunosuppressive effects on the tumor microenvironment.

    Overall, the trial wasn't as large as they'd hoped, because only 17-18% of the 342 patients were even eligible to enroll, ie most cancers did not express PDL-1. Those who were able to join and add Keytruda to chemo saw just a little benefit, ( PFS of 6.7 v 6 months). Overall, 26% of those adding Keytruda made it out to one year, compared to 20% of those only taking chemo, and 14% made it two years, compared to 3.5% without immunotherapy. So the benefit was modest but the signal was clear.

    https://www.esmo.org/insights-by-esmo/all-news/is-there-an-early-role-for-immunotherapy-in-endocrine-refractory-breast-cancer

    Multiple biomarkers/drugs/treatments have been reported to boost the response to Keytruda in the past decade, including screening for those with high tumor mutation burden, combining the immunotherapy with histotripsy, taking the Repatha cholesterol drug (which increases cancer neoantigen expression) , taking an SSRI anti-depressant, and even getting a Covid vaccine (which increases PDL-1 expression). Hopefully more trials will look at trying immunotherapy combinations for ER-positive breast cancers, but things are moving awfully slowly…

  • bsandra
    bsandra Posts: 1,106

    Dear @cure-ious , for all these years that I have followed Keytruda, it was a strange drug - in some cases it worked wonders but there are many clinical trials that it failed to show good results even in PD-L1 patients… we need a more effective version of such drug:/ Hugs, Saulius

  • cure-ious
    cure-ious Posts: 3,194
    edited October 25

    Hi @bsandra

    Good to hear from you! I hope your wife continues along swimmingly!!!

    It really feels like the field has just given up on immunotherapy for ER-positive MBC, but we desparately need another line and this has such upside potential. A study of a handful of the rare patients with high TMB found that 60% responded to immunotherapy, so can't they find a drug that mimics high neoantigen expression? Repatha cholesterol injections have been reported to do that, but there haven't been any studies. Are they even clear about why ER signaling makes such an immunosuppressive microenvironment?

    And what about those vaccines like the one your wife got? Well, at least the research on vaccines for Her2+ cancers like hers continues at rapid pace:

    https://link.springer.com/article/10.1186/s13046-026-03789-1

    Anyway, those of us with more-or-less endocrine-resistant ER+ cancers persist, an awful lot of us in the same boat!!!

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